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Introduction: The safety and efficacy of the extended half‐life factor VIII (FVIII) product damoctocog alfa pegol (BAY 94‐9027, Jivi®) has been demonstrated in the PROTECT VIII Kids study (NCT01775618), where male previously‐treated patients (PTPs) aged <12 years old with severe haemophilia A and ≥ 50 exposure days (EDs) were treated prophylactically. The PROTECT VIII Kids extension study assessed the long‐term safety and efficacy of damoctocog alfa pegol in the same population. Aim: To evaluate the long‐term impact of damoctocog alfa pegol in a post hoc subgroup analysis of adolescent patients in the PROTECT VIII Kids study and its extension from 12th birthday onwards. Methods: The current analysis included PTPs aged ≥12 years old, who remained in the extension for ≥6 months following their 12th birthday. The observation period was defined as the time from 12th birthday to the end of the extension period; all data from this birthday were included whether in the main study or extension phase. The main efficacy variable was annualised bleeding rate (ABR) and the main safety variable was the frequency of inhibitor development. Results: This subgroup analysis comprised 25 patients. Median observation time after 12th birthday was 3.2 years. Median total/joint/spontaneous ABRs in the observation period were 1.7/0.7/0.3, respectively. Safety findings were consistent with those reported for the overall study population; no confirmed FVIII inhibitors or anti‐drug antibodies were reported. Conclusions: Damoctocog alfa pegol is efficacious with a favourable safety profile in adolescents with haemophilia A, supporting its long‐term use in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra‐rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)‐cleaving metalloprotease. The plasma‐derived factor VIII/VWF Koate (FVIII/VWFKoate) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. Aim: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. Methods: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. Results: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5–6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate. There was one AE (unspecified) attributed to FVIII/VWFKoate. Conclusion: These data suggest that FVIII/VWFKoate is a safe and well‐tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self‐ or caregiver‐administration. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first‐year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership. Methods: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort. We used a multinomial logistic regression to predict the odds of class membership based on the above predictors. We fitted a survival model to assess whether there were differences in the rate of dose escalation across the groups. Results: We identified three distinct classes of trajectory: persistently low, moderately increasing and rapidly increasing joint scores. By multinomial regression, we found that only age at first index joint bleed predicted rapidly increasing joint scores. The rapidly increasing joint score class group moved through dose escalation significantly faster than the other two groups. Conclusions: Using tailored prophylaxis, boys with SHA follow one of three joint health trajectories. By using knowledge of disease trajectories, clinicians may be able to adjust treatment according to a subject's predicted long‐term joint health and institute cost‐effective programmes of prophylaxis targeted at the individual subject level. [ABSTRACT FROM AUTHOR]

Introduction: BAY 94‐9027 (damoctocog alfa pegol; an extended half‐life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged <12 years with severe haemophilia A in the PROTECT VIII Kids study (NCT01775618). Aim: To evaluate the long‐term safety of BAY 94‐9027 in PTPs aged <12 years at enrolment. Methods: In the PROTECT VIII Kids study, boys <12 years with severe haemophilia A were enrolled in two age cohorts (6–<12 years and <6 years) and treated prophylactically twice weekly, every 5 days or every 7 days, with BAY 94‐9027 for ≥50 exposure days (EDs). Patients who had completed ≥50 EDs and ≥6 months in the main study or 12‐week safety expansion study were eligible to participate in the extension. Primary safety variable was frequency of inhibitor development; main efficacy variable was annualised bleeding rate (ABR). Results: Of 73 PTPs from the main/expansion studies, 59 (81%) entered the extension phase for a median (range) duration of 5.0 (0.4–5.9) years. Overall, 39 patients completed ≥5 years of treatment. No patients developed FVIII inhibitors/anti‐PEG antibodies, and two patients aged <6 years discontinued. Median ABR for total bleeds was 1.5 (<6 years) and 1.9 (6–<12 years). Total ABR improved in the extension vs. the main study. In the last 12 months of treatment, median spontaneous ABR was 0.0 in both age groups. Conclusions: BAY 94‐9027 showed long‐term safety and efficacy for the prevention and treatment of bleeds in younger and older paediatric patients with severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: BAY 94‐9027, a site‐specifically PEGylated, B‐domain‒deleted recombinant factor VIII (FVIII) with extended half‐life, demonstrated efficacy for bleed prevention and treatment in previously treated adolescents and adults with severe haemophilia A. Aim: To assess BAY 94‐9027 in children with severe haemophilia A. Methods: In the two‐part PROTECT VIII Kids study, boys <12 years with <1% FVIII and >50 exposure days (EDs) to FVIII were enrolled in two cohorts (<6 years; 6‐<12 years) and treated with BAY 94‐9027 prophylaxis twice‐weekly, every 5 days, or every 7 days at physician discretion for ≥50 EDs (Part 1) or twice‐weekly for 12‐weeks (Part 2). Annualized bleeding rate (ABR) was a primary efficacy endpoint; FVIII inhibitor development was the primary safety variable. Results: At study completion, 25 patients had been treated twice‐weekly, 28 in the every‐5‐day group, and 8 in the every‐7‐day group. Median ABR for all bleeds was 2.9 (Part 1) and 2.4 (Part 2) and similar in younger and older patients; median ABR for joint bleeds was 0 for both cohorts. In the last 90 days' treatment, median ABR was 0 for younger and older patients (Part 1). Of 149 reported bleeds, 93% were treated with ≤2 infusions. Twelve patients, the majority <6 years (n = 11), discontinued due to apparent loss of efficacy or hypersensitivity. No FVIII inhibitors developed. Conclusions: In PROTECT VIII Kids, which allowed tailoring of prophylaxis to individual clinical response, BAY 94‐9027 was efficacious for bleed prevention and treatment in previously treated children with severe haemophilia A. [ABSTRACT FROM AUTHOR]